Evaluation of the clinical impact of repeat application of hydrogel-forming microneedle array patches

Rehan Al-Kasasbeh,Aaron J Courtenay,Ryan F Donnelly,Eneko Larrañeta,Aaron J Brady,Donal O'Kane,Maelíosa T C Mccrudden,Stephen Liggett

doi:10.1007/s13346-020-00727-2

Abstract

Hydrogel-forming microneedle array patches (MAPs) have been proposed as viable clinical tools for patient monitoring purposes, providing an alternative to traditional methods of sample acquisition, such as venepuncture and intradermal sampling. They are also undergoing investigation in the management of non-melanoma skin cancers. In contrast to drug or vaccine delivery, when only a small number of MAP applications would be required, hydrogel MAPs utilised for sampling purposes or for tumour eradication would necessitate regular, repeat applications. Therefore, the current study was designed to address one of the key translational aspects of MAP development, namely patient safety. We demonstrate, for the first time in human volunteers, that repeat MAP application and wear does not lead to prolonged skin reactions or prolonged disruption of skin barrier function. Importantly, concentrations of specific systemic biomarkers of inflammation (C-reactive protein (CRP); tumour necrosis factor-α (TNF-α)); infection (interleukin-1β (IL-1β); allergy (immunoglobulin E (IgE)) and immunity (immunoglobulin G (IgG)) were all recorded over the course of this fixed study period. No biomarker concentrations above the normal, documented adult ranges were recorded over the course of the study, indicating that no systemic reactions had been initiated in volunteers. Building upon the results of this study, which serve to highlight the safety of our hydrogel MAP, we are actively working towards CE marking of our MAP technology as a medical device.

Highlights

Hydrogel-forming microneedle array patches (MAPs, Fig. 1) are based on arrays of projections less than 1 mm in height perpendicularly arranged upon a flat baseplate, where both the projections and the baseplate are comprised of chemically cross-linked hydrophilic polymer matrices [1]
We have shown that such MAPs can be reproducibly inserted into their own skin by human volunteers, even when the patch size is much greater than the 1–2 cm2 size typical of microneedle systems [14,15,16]
We have shown that repeat insertion into mouse skin in vivo, followed by subsequent retention for 24 h did not lead to disturbance in skin appearance, skin barrier function or biomarkers of infection, immunity, inflammation or allergy [19]

Summary

Introduction

Hydrogel-forming microneedle array patches (MAPs, Fig. 1) are based on arrays of projections less than 1 mm in height perpendicularly arranged upon a flat baseplate, where both the projections and the baseplate are comprised of chemically cross-linked hydrophilic polymer matrices [1]. We have made extensive use of this system for transdermal delivery of high doses of both small molecules and macromolecular agents [1], with our data suggesting that appropriately sized patches could be used to administer daily doses of tens or hundreds of milligrammes per day in humans [2]. This creates the possibility for a substantial expansion of the range of types of drug that could be successfully delivered transdermally

Methods

Results

Conclusion